Bottom Line:
Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action.We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer.We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

ABSTRACTThe emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

Mentions:
As a synthesis, we highlight two major, functionally different inflammatory networks: a network of inflammatory mediators driving (antigen)-specific anti-tumor immunity to inhibit tumor development (19, 20) and a nexus of cytokines supporting chronic, unspecific, pro-tumorigenic inflammation in the CRC microenvironment (Figure 1), which is associated with a disruption of the intestinal barrier and invasion by microbial products (21). It is likely that the balance between these two opposite inflammatory networks within the tumor stroma determines the course of CRC development. We also propose that these different groups of cytokines may be used as biomarkers to strengthen the diagnostic based on the Immunoscore, and that they represent targets for the design of therapeutic approaches.

Mentions:
As a synthesis, we highlight two major, functionally different inflammatory networks: a network of inflammatory mediators driving (antigen)-specific anti-tumor immunity to inhibit tumor development (19, 20) and a nexus of cytokines supporting chronic, unspecific, pro-tumorigenic inflammation in the CRC microenvironment (Figure 1), which is associated with a disruption of the intestinal barrier and invasion by microbial products (21). It is likely that the balance between these two opposite inflammatory networks within the tumor stroma determines the course of CRC development. We also propose that these different groups of cytokines may be used as biomarkers to strengthen the diagnostic based on the Immunoscore, and that they represent targets for the design of therapeutic approaches.

Bottom Line:
Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action.We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer.We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

ABSTRACTThe emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.